In-Depth Analysis of the Mechanism of Astaxanthin Succinate Diester in Reducing Ulcerative Colitis in C57BL/6J Mice Based on Microbiota Informatics

Abstract

This paper aims to explore the effect and mechanism of water-soluble astaxanthin succinate diester (Asta-SD) on ulcerative colitis (UC) induced by dextran sodium sulfate in zebrafish and C57BL/6J mice. Asta-SD was synthesized with hydrophilic fatty acid succinic anhydride and the hydroxyl groups at the ends of F-Asta were synthesized by esterifying. Through the construction of a zebrafish intestinal inflammation model, it was found that Asta-SD could effectively reduce the levels of ROS and increase the number of healthy intestinal lysosomes in zebrafish. After continuous gavage of Asta-SD for seven days, the body weight, disease activity index, colonic length, colonic histopathology, expression of inflammatory factors, and intestinal flora of the mice were measured. The results showed that Asta-SD could significantly alleviate weight loss and colonic shrinkage, as well as reducing pro-inflammatory cytokines and recess injury in UC mice. The 16S rRNA gene sequencing showed that Asta-SD significantly increased the beneficial bacteria (Lactobacillus, Anaerotruncus) and decreased the relative abundance of pathogenic bacteria, effectively maintaining intestinal microbiota homeostasis in mice. Based on Pearson analysis, Bacteroides, Parabacteroides, and Butyrimionas were expected to be associated with the significant difference in the expression of inflammatory factors between the UC and the corresponding host. Thus, Asta-SD significantly improves UC and maintains intestinal microbiota homeostasis.

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“…Asta-SD decreased the gene expression levels of TNF-α, IL-6, and IL-1β. Furthermore, this study also found that the abundance of Bacteroides, Parabacteroides, and Butyrimionas were positively correlated with the gene expression of IL-6 [162]. These findings suggest the Asta-SD ameliorates inflammation in an animal model of UC via the maintenance of intestinal microbiota homeostasis.…”

“…Ax-Alg was demonstrated to reduce the level of LPS and translocate it from the intestinal lumen to the blood in DSS-induced colitis, suggesting that astaxanthin may attenuate the inflammatory response in colitis by inhibiting LPS expression or translocation [160]. A recent study reported that astaxanthin succinate diester (Asta-SD) counteracted the downward trend of the F/B ratio and reduced the abundance of Bacteroides, Geobacter, Alistipes, Butyrimionas, and Parabacteroides in mice with DSS-induced colitis [162]. Treatment with Asta-SD also promoted the proliferation of beneficial bacteria Anaerotruncus and Lactobacillus.…”